Mucosal Priming with a Recombinant Influenza A Virus-Vectored Vaccine Elicits T-Cell and Antibody Responses to HIV-1 in Mice
| Autor: | Ping He, Ying Feng, Ting Li, Caijun Sun, Liqiang Feng, Xuehua Zheng, Jinlin Wang, Fengyu Hu, Min Liao, Ling Chen, X.L. Ye, Feng Li, Weiqi Deng, Lujie Han, Tao Shu, Pingchao Li, Yali Zheng |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
viruses
HIV Core Protein p24 HIV Infections CD8-Positive T-Lymphocytes HIV Antibodies Antibodies Viral medicine.disease_cause Epitope Mice Immunogenicity Vaccine Influenza A Virus H1N1 Subtype 0302 clinical medicine Influenza A virus 030212 general & internal medicine AIDS Vaccines Immunity Cellular Mice Inbred BALB C Vaccines Synthetic 0303 health sciences biology Vaccination virus diseases Genes gag medicine.anatomical_structure Female Bronchoalveolar Lavage Fluid Lymphoid Tissue T cell Immunology Immunization Secondary Microbiology Virus Adenoviridae Viral vector 03 medical and health sciences Immune system Antigen Virology Vaccines and Antiviral Agents medicine Animals Immunity Mucosal 030304 developmental biology Influenza A Virus H3N2 Subtype Immunoglobulin A Immunoglobulin G Insect Science HIV-1 biology.protein Neuraminidase |
| Zdroj: | J Virol |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.00059-21 |
| Popis: | Recombinant influenza A viral (IAV) vectors are potential to stimulate systemic and mucosal immunity, but the packaging capacity is limited and only one or a few epitopes can be carried. Here, we report the generation of a replication-competent IAV vector that carries a full-length HIV-1 p24 gene linked to the 5′-terminal coding region of the neuraminidase segment via a protease cleavage sequence (IAV-p24). IAV-p24 was successfully rescued and stably propagated, and P24 protein was efficiently expressed in infected mammalian cells. In BALB/c mice, IAV-p24 showed attenuated pathogenicity compared to that of the parental A/PR/8/34 (H1N1) virus. An intranasal inoculation with IAV-p24 elicited moderate HIV-specific cell-mediated immune (CMI) responses in the airway and vaginal tracts and in the spleen, and an intranasal boost with a replication-incompetent adenovirus type 2 vector expressing the HIV-1 gag gene (Ad2-gag) greatly improved these responses. Importantly, compared to an Ad2-gag prime plus IAV-p24 boost regimen, the IAV-p24 prime plus Ad2-gag boost regimen had a greater efficacy in eliciting HIV-specific CMI responses. P24-specific CD8(+) T cells and antibodies were robustly provoked both systemically and in mucosal sites and showed long-term durability, revealing that IAV-p24 may be used as a mucosa-targeted priming vaccine. Our results illustrate that IAV-p24 is able to prime systemic and mucosal immunity against HIV-1 and warrants further evaluation in nonhuman primates. IMPORTANCE An effective HIV-1 vaccine remains elusive despite nearly 40 years of research. CD8(+) T cells and protective antibodies may both be desirable for preventing HIV-1 infection in susceptible mucosal sites. Recombinant influenza A virus (IAV) vector has the potential to stimulate these immune responses, but the packaging capacity is extremely limited. Here, we describe a replication-competent IAV vector expressing the HIV-1 p24 gene (IAV-p24). Unlike most other IAV vectors that carried one or several antigenic epitopes, IAV-p24 stably expressed the full-length P24 protein, which contains multiple epitopes and is highly conserved among all known HIV-1 sequences. Compared to the parental A/PR/8/34 (H1N1) virus, IAV-p24 showed an attenuated pathogenicity in BALB/c mice. When combined with an adenovirus vector expressing the HIV-1 gag gene, IAV-p24 was able to prime P24-specific systemic and mucosal immune responses. IAV-p24 as an alternative priming vaccine against HIV-1 warrants further evaluation in nonhuman primates. |
| Databáze: | OpenAIRE |
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